Mészáros J, Villanova L, Pappano A J
Department of Pharmacology, University of Connecticut Health Center, Farmington 06032.
J Mol Cell Cardiol. 1988 Jun;20(6):481-92. doi: 10.1016/s0022-2828(88)80075-0.
In ventricular muscle, 1-palmitoyl carnitine (1-PC) acted like calcium ions to shift the voltage-dependent inactivation of excitatory ion currents to less negative potentials. We proposed that 1-PC affected ion current kinetics by reducing surface negative charge. This hypothesis was tested in cell electrophoresis experiments where the electrophoretic mobility (EPM) of erythrocytes was measured in the absence and presence of test ligands. Calcium (0.18 to 3.6 mM) or 1-PC (10(-7) to 10(-6) M) reduced erythrocyte EPM in a concentration-dependent manner; the maximum reduction of EPM by either ligand was approximately 40%. In the presence of calcium, 1-PC produced a smaller decrement of EPM as expected from an occlusive interaction. Treatment of erythrocytes to remove sialic acids not only predictably reduced EPM but also diminished the ability of 1-PC and calcium to do so. These results indicate that the surface negative charge of sialic acid carboxyl groups is an important determinant both of erythrocyte EPM and of erythrocyte interaction with either 1-PC or calcium. The findings are consistent with the surface charge hypothesis for 1-PC action. We propose that 1-PC is not a neutral molecule at the cell surface but is able to neutralize surface negative charge by electrostatic interaction between the sialic acid carboxyl groups and the 1-PC quaternary ammonium moiety on the one hand and between the 1-PC carboxyl group and counterions near the membrane surface.
